Coated medicaments



nited 3153035 Patent Ofiice Patented June, 14,, 1,960

COATED MEDICA'MENT S Gordon D. Hiattand John Emerson, Rochester, N'.Y.,

assignors'to-Eastman- Kodak Company, Rochester, N.Y.', a corporation of.New. Jersey:

No Drawing. Filed Feb. 3, 1958, Ser. No. 712,619

5 Claims. (Cl. 167-821 This application relates to medicament tabletshaving a coating selected from certain cellulose derivatives.

Pharmaceutical preparations or medicines which are solids are commonlydispensed in the form of compressed units referred to as pills ortablets. These tablets are prepared by processing the medicament inpowder form in tablet compressing machines of any suitable type. It hasbeen customary to coat the compressed pharmaceutical tablets thusobtained by tumbling them in a coating pan which involves the successiveapplications of sugar syrup, sometimes with fillers such as chalk or thelike, While the tablets are being tumbled in the coating pan. Thisprocedure results in building up a continuous coating of sugar upon thesurface of the tablets, making those tablets easy to handle and readilyadministered. This overcoating gives the tablets a smooth surface whichis easily polished, and prevents chipping of the tablets duringhandling. The application of such coatings, however, to thepharmaceutical tablets is time consuming because the water employed as asolvent for the sugar to form the coating composition must beevaporated. Tablets so coated are water susceptible and are subject tospoilage whenever wet accidentally.

One object of our invention is to provide a coating for medicamenttablets which can be applied thereto from a solution of a cellulosederivative in a low-boiling solvent, susceptible to rapid evaporation,whereby a smooth surface is formed on the tablets. Another object of ourinvention is to provide coated medicaments in which the coating thereofis resistant to water. A further object of our invention is to provide acellulose derivative coating for medicaments, which coating willdisintegrate in the presence of dilute aqueous acid such as isencountered in the stomach. Other objects of our invention will appearherein.

The above objects are met by coating medicament tablets such as ofaspirin, acetanilide, dried yeast, compounded vitamins, mineral saltssuch as bismuth subnitrate, calcium carbonate, ferrous lactate,magnesium oxide or potassium iodide, or any solid medicament ormedicament compounded to a solid form with a solution of an alkyl aminoacylate of a cellulose derivative, for example, cellulose acetatediethyl amino acetate. Cellulose derivatives of this type are dissolvedin volatile organic solvents such as acetone or a low-boilingchlorinated hydrocarbon and applied to medicament tablets. Uponsubjecting the tablets to drying conditions such as a current of warmair or a vacuum treatment, the coating quickly loses solvent and thereresults tablets having a smooth, waterresistant surface which is alsoresistant to the ordinary handling to which medicament tablets aresubjected. Tablets coated in this fashion remain unchanged in water, butthe coating thereon readily disintegrates in dilute aqueous acid such asgastric juice which permits the release of the medicament shortly afterits entrance into the stomach.

Our invention also includes the use of alkyl amino 2. acetates ofcellulose derivatives; asa binderin the: prep; aration of medicamentproducts. For instance, some, of the solution of the-cellulose alkyl1amino. acetate;c om-. pound maybe milledor kneaded with medicament .insolid form to form a mass of fairly uniform composition which isthengiven formjor shapesuch asby extrusion and then dried;

The amino acetates of cellulose derivativeswhich. are. useful-are .thedimethylamino acetates, the monomethyl amino acetates, the-v diethyl,amino. acetates, the, dinormal propylanddiisopropyl aminoacetates, the.dibutyl amino acetates, the morpholine acetates; and the.piperidine,ace=tates of cellulose derivatives. As a matter of fact, the derivatives ofany of the amines having not more than 8 carbon atoms are useful. Thecellulose derivatives to which these amino acetate groups may beimparted to obtain compounds useful for coating medicament tablets arecellulose, cellulose acetate, cellulose acetate propionate, celluloseacetate butyrate, ethyl cellulose, and hydroxyethyl cellulose. Theamount of substitution should be such that in the making of thecellulose derivatives there should be at least 4 /2-25% of chlorine inthe compound when in the chloroacetate stage of preparation. It isdesirable for best results, when the higher amines are supplied that thesubstitution be well above the minimum given. The following exampleshows the preparation of cellulose compounds useful for coatingmedicament tablets in accordance with our invention. This procedure maybe followed by the preparation of the cellulose compounds which havebeen mentioned above as useful for this purpose:

A hydrolyzed cellulose acetate was treated with chloracetic acid to givea cellulose acetate chloroacetate having a chlorine content of 8.4% Thiscellulose acetate chloroacetate was reacted with diethyl amine wherebythe chlorine was replaced with diethyl amino groups. The celluloseacetate diethyl amino acetate obtained had a nitrogen content of 2.4%nitrogen.

The preparation of compounds of this type is not our invention, but isthe invention of John W. Mench and Brazelton Fulkerson and is describedin their application Serial No. 619,681, filed Nov. 1, 1956, now PatentNo. 2,861,068. That disclosure may be referred to for details of themethod of preparing compounds useful for coating medicaments to formproducts in accordance with our invention.

The cellulose acetate diethyl amino acetate formed as described abovewas dissolved in acetone to give a solution of 15% concentration. Thissolution was added portionwise to compressed sodium chloride tablets,which tablets were tumbled to distribute the solution thereon. Atintervals an air jet was applied to remove the acetone from the tablets.The application of the coating of cellulose acetate diethyl aminoacetate to the tablets took less than one hour. The tablets thus coatedwhen immersed in water did not change form after two hours immersion.However, these tablets when treated with dilute aqueous hydrochloricacid simulating gastric juice disintegrates the coating and allowsrelease of the salt to the solution. Our invention is applicable to anysolid medicament tablets in which the medicament is intended for releasein the stomach when administered in medication procedures.

Another method of operation is to use the cellulose derivative aminoacylate as a binder with a medicament capable of plasticizing orsoftening the binder, especially when the composition is heated. Othermedicaments can be added to this two component mixture whether theysoften the hinder or not. They may actually be the main therapeuticagent and are enclosed by the plasticized binder composition whic forexample, may be cellulose acetate diethylamino acetate and acetylsalicylic acid or aspirin.

""We'claim:

V 1. A medicament composition comprising tablets of a 'solid formmedicament compounded with an alkyl amino [acetate of a cellulosederivative ;the alkyl amino groups of which have no more than ,8 carbonatoms; 2; Medicament tablets containing thereon a coating of an 'falkylamino acetate .01? a cellulose compound the alkyl amino groups of whichhave no more than 8 carbon atoms. a V I 3; A medicamentcompositioncomprising tablets of a solidsmedicamenthaving thereon a coating ofcellulose acetate diethyl amino acetate.

4. Sodium chloride tablets. containing a coating, of

cellulose acetate diethyl amino acetate.

' '5. A: method of preparing a medicament composition 15 which comprisestumbling compressed units of medicament with 9. 80111110551 an alkylamino acetate of a cel- V lulose compound thealkyl amino groups of whichhave no more than 8 carbon atoms in a volatile solvent and followed byremoval of the volatile solvent from the composition.

References Cited-in the file of this patent

1. A MEDICAMENT COMPOSITION COMPRISING TABLETS OF A SOLID FROMMEDICAMENT COMPOUND WITH AN ALKYL AMINO ACETATE OF A CELLULOSEDERIVATIVE THE ALKYL AMINO GROUPS OF WHICH HAVE NO MORE THAN 8 CARBONATOMS.